Otto wolfes and hoest maeder



Patented Apr. 21, 1925.

UNITED STATES PATENT QFFICE.

OTTO WOLFES AND HORST MAEDER, OF DARMSTADT, GERMANY.

PROCESS OF MANUFACTURE OF ID-w- AND L-d-COCAINE.

No Drawing.

6 new and useful Improvements in the Process of Manufacture of (Ma andZap-cocaine, of which the following is a cleaiyiull, and exactdescription.

VVillstiitter and Bode (Annalen, 326 (1903), p. 4-2), and lVillstEitterand Bommer (Annalen, 422 (1921), p. 15) have prepared a racemic form ofcocaine, of which it was thought, on account of its properties, that itbelonged to the pseudo-series, but attempts to verify this view byconverting it into the d-ql-cocaine which is already known, failed. Itwas impossible by treatment with optically active acids or by feeding itto Pem'cz'lz'um glance-m, to split the racemic form into its opticallyactive components.

It was then found that optically active Lil-000211118 may be obtained bysplitting up the corresponding racemic ecgonine ester and thenbenzoylating the optically active one.

Example 1.Dissolve 2.5 parts (Ll-q)- ecgonine methylester, preparedaccording to Willstatter and Bode, and 3.8 parts(l-oabromocamphor-(i-sulphonic acid (Armstrong and Lowry, Proceedings ofthe Chem. Soc, no. 240) in a few 0. cm. of absolute alcohol and treatwith acetic ether. Eventually, cofiin-lid crystals are formed which havea melting point of 198 C. and

From these crystals cl-qz-ecgonine methylester may be separated in theusual manner. It is identical with the natural cZ-ecgonine methylesterwhich has a melting point of 115 0.

Just as from the natural plant product, clay-cocaine may be obtainedfrom this synthetic product by benzoylation which is carried out asfollows:

The (l-zP-ecgOnine methylester is dissolved in a little benZol andheated for two hours on the water-bath, with reflux condenser attached,with a little more than calculated quantity of benzoic anhydride, carebeing Application filed December 3, 1923.

Serial No. 678,337.

taken to prevent access of moisture. After evaporation ot the solvent,the residue is treated with ether and ethereal hydrochloric acid. Theethereal solution which con tains benzoic acid is then decanted from thesolid hydrochloride. The salt is next washed in ether, taken up inwater, precipitated by adding sodium carbonate and final ly the base isextracted with ether.

The alkaloid, when purified by washing in water and recrystallizationfrom petrol ether, has a melting point of 45 C. Its hydrochloride, whichis only with difiiculty soluble in water, melts at 205 C. and in 5 percent solution it has an optical activity of The base is identical withthe natural (H1- cocaine from plants.

Example 2.Thirty parts of the same racemic ecgonine ester and 47 partsof aZ- zbromocamphor-Wsulphonic acid (Kipping and Tope, Journ. of theChem. Soc. 67, p. 856) are dissolved in parts of hot methylalcohol andslowly allowed to cool. dcbromocamphor-w-sulphonic acid Z-gb-ecgd ninemethylester crystallizes out, which has a melting-point of 243 C. and anoptical activity of and from which Z-tP-ecgonine methylester,melting-point of 115 (1., may be obtained. Dissolved in 10 per centmethyl alcohol, it shows an optical activity of The l-dg-cocaine meltsat 45 6.; the hydrochloride, which is with difiiculty soluble in water,has a melting-point of 205, and in 5 per cent aqueous solution shows anoptical activity of egg-43.

Emamplc 3.Fifty parts of the racemic ecgonine ester and parts of naturalmalic acid are dissolved in 100 parts of methyl alcohol. The crystalswhich are subsequently formed consists of Z-inalic acid-Z-dg-ecgoninemethylester. It has a melting-point of 176 C. and shows an opticalactivity of a 1s.2. It issoluble with difiiculty only. From the liquorcZ-malic-cZ-qi-ester may be obtained, which has a melting-point of 1492C.

Claim.

Process of manufacture 01. (Z-qiand Z-ilicocaine by converting(Z-Z-it-ecgonine methylester by means of optically active acids, intothe corresponding salts, separating the Z- IJ-salt from the(Z-llJ-Sflli] by fractional crystallization of the latter, and isolatingand benZoylating-the bases in the usual manner.

In testimony whereof we have hereunto signed our names in the presenceof the two subscribing witnesses.

., DR. OTTO.WOLFES.

DR, HORST MAEDER. \Vitnesses G; FLEsoH, JANE: GIUSTI.

